Skip Navigation

Cardiovascular Research 1999 43(3):755-761; doi:10.1016/S0008-6363(99)00170-4
© 1999 by European Society of Cardiology
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow E-letters: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when E-letters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Nguyen, T.-D.
Right arrow Articles by Thorin, E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nguyen, T.-D.
Right arrow Articles by Thorin, E.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Copyright © 1999, European Society of Cardiology

Effects of endothelin receptor antagonists and nitric oxide on myogenic tone and {alpha}-adrenergic-dependent contractions of rabbit resistance arteries

Thanh-Dung Nguyen, Philippe Véquaud and Eric Thorin*

Institut de Cardiologie de Montréal, Centre de Recherche, 5000, Rue Bélanger Est, Montréal, Que., Canada H1T 1C8

* Corresponding author. Tel.: +1-514-376-3330, ext: 3589; fax: +1-514-376-1355 thorin{at}icm.umontreal.ca

Regulation of vascular contractions by endothelium-derived endothelin-1 (ET-1) and nitric oxide (NO) may vary depending on the stimulus. Objectives: To investigate if ET-1 receptor stimulation and NO contributed to a similar extent to the regulation of pressure- and {alpha}-adrenergic receptor (AR) agonist-induced smooth muscle contraction. Methods: Rabbit mesenteric arteries (150–200 µm) were isolated, cannulated and pressurized. Changes in diameter were recorded as a function of the perfusion pressure (PP) or {alpha}-AR agonist addition at a PP of 60 mmHg. All experiments were performed in the presence of indomethacin (10 µmoll–1). Results: At a PP of 60 mmHg, myogenic tone (MT) developed to represent 17±1% of the minimal diameter. The magnitude of the MT was increased by 140% (P<0.05) by the inhibition of NO production with N{omega}-nitro-L-arginine (L-NOARG). Bosentan, an ETA/B receptor antagonist, and BQ 123, a selective ETA receptor antagonist, decreased (P<0.05) MT either alone or in combination with L-NOARG by {approx}30%. Phenylephrine (Phe), an {alpha}1-AR agonist, induced contraction; the sensitivity to Phe (pD2, 6.2±0.2) was unaffected by bosentan or BQ 123 alone but increased (P<0.05) by L-NOARG (pD2, 7.3±0.5). Further addition of bosentan or BQ 123 restored the sensitivity to Phe to its control value. Oxymetazoline (OXY), an {alpha}2-AR agonist, induced contraction; the sensitivity to OXY (pD=2, 7.7±0.2) was unaffected by L-NOARG, bosentan or BQ 123. Conclusion: Our results indicate that pressure-induced tone is independently regulated by endothelium-derived NO and ET-1. In contrast, {alpha}1-AR stimulation-induced tone is sensitive to ET-1 in the absence of NO, whereas occupation of {alpha}2-AR mediates a contraction unregulated by the endothelium.

KEYWORDS AR, adrenergic receptor; EDHF, endothelium-derived hyperpolarizing factor; ET-1, endothelin-1; L-NOARG, N{omega}-nitro-L-arginine; MT, myogenic tone; NO, nitric oxide; OXY oxymetazoline; Phe, phenylephrine; PP, perfusion pressure; PSS, physiological salt solution


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.